CN101570550A - Method for synthesizing chiral ferrocene diphosphine ligand - Google Patents
Method for synthesizing chiral ferrocene diphosphine ligand Download PDFInfo
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Abstract
本发明涉及手性二茂铁类双膦配体的合成方法。手性二茂铁类双膦配体的合成方法是以二茂铁为原料，经付－克反应后得乙酰二茂铁，乙酰二茂铁经还原、酯化、胺化得N，N－二甲基胺乙基二茂铁，用手性酸对N，N－二甲基胺乙基二茂铁进行拆分，得到R－N，N－二甲基胺乙基二茂铁的手性酸盐，解析R－N，N－二甲基胺乙基二茂铁手性酸盐得光学纯的R－N，N－二甲基胺乙基二茂铁，用得到的R－N，N－二甲基胺乙基二茂铁与有机锂碱反应后，加入二烃基1氯化膦反应得1－S－二烃基1膦－2－R－N，N－二甲胺基二茂铁，进一步与另一个二烃基2膦反应得手性双膦配体1－S－二烃基1膦基－2－R－二烃基2膦基二茂铁。在该方法中简化了操作，生产成本低，可用于工业化生产。The invention relates to a synthesis method of a chiral ferrocene bisphosphine ligand. The synthesis method of chiral ferrocene-type diphosphine ligands is to use ferrocene as raw material, after the Friedel-Crafts reaction, acetyl ferrocene is obtained, and the acetyl ferrocene is reduced, esterified and aminated to obtain N, N- Dimethylaminoethyl ferrocene, use chiral acid to resolve N, N-dimethylaminoethyl ferrocene, and obtain the chirality of R-N, N-dimethylaminoethyl ferrocene salt, analyze RN, N-dimethylaminoethyl ferrocene chiral acid salt to obtain optically pure RN, N-dimethylaminoethyl ferrocene, use the obtained R-N , N-dimethylaminoethyl ferrocene reacts with organic lithium base, and then adds dihydrocarbyl 1 phosphine chloride to react to obtain 1-S-dihydrocarbyl 1 phosphine-2-R-N, N-dimethylamino di Ferrocene is further reacted with another dihydrocarbyl 2 phosphine to obtain a chiral bisphosphine ligand 1-S-dihydrocarbyl 1 phosphino-2-R-dihydrocarbyl 2 phosphinoferrocene. In the method, the operation is simplified, the production cost is low, and it can be used in industrialized production.
Description
Technical field
The present invention relates to a kind of synthetic method of chiral ferrocene diphosphine ligand, it belongs to technical field of organic chemistry, also belongs to the pharmaceutical chemistry technical field.
Background technology
Chiral ferrocene diphosphine ligand is the important part in the asymmetric catalytic hydrogenation Preparation of Catalyst, it has been widely used in the asymmetric hydrogenation, be the model of asymmetric catalysis in industrial application, since the seventies, be the focus of domestic and international pharmaceutical industries concern and the focus of research always.In asymmetry catalysis, catalyst ligand commonly used has biphosphine ligand, and most of biphosphine ligands are easily oxidized, and ferrocene diphosphine ligand is then relatively stable, has been widely used in the extensive asymmetric catalytic hydrogenation reaction.
Document (Bull.Chem.Soc.Jpn., 53, in the reported method be that raw material is synthetic through multistep 1138-1151) with the ferrocene, adopted repeatedly chromatographic separation purifying in the route, operation inconvenience.So people are seeking simply, safety, production method that cost is low, thereby reduce production costs, and promote the well-being of mankind always.
Summary of the invention
A kind of method is simple, productive rate is high, the synthetic method of the chiral ferrocene diphosphine ligand of the low industrialization of cost but the purpose of this invention is to provide.
To achieve these goals; technical scheme of the present invention is: the synthetic method of chiral ferrocene diphosphine ligand; be from ferrocene (I) for raw material through acetylize; reduction; esterification generates compound acetyl oxygen ethyl dicyclopentadienyl iron (IV); compound acetyl oxygen ethyl dicyclopentadienyl iron (IV) generates N with the dimethylamine replacement(metathesis)reaction; N dimethylamine ethyl dicyclopentadienyl iron (V); N; the 2-R-N that N dimethylamine ethyl dicyclopentadienyl iron (V) splits by chiral acid; N dimethylamine ethyl dicyclopentadienyl iron (V) and 2-S-N; N dimethylamine ethyl dicyclopentadienyl iron (V); 2-R-N, N dimethylamine ethyl dicyclopentadienyl iron (V) and lithium alkali reaction get the lithium salts of ferrocene, again with dialkyl
1The phosphonium chloride reaction generates the 1-S-dialkyl of the configuration that has comparative advantage
1Phosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI), 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI) and dialkyl
2The phosphine exchange generates biphosphine ligand (VII) 1-S-dialkyl
1Phosphino--2-R-dialkyl
2The phosphino-ferrocene.
Major technique advantage of the present invention is: do not needed through column chromatography to compound (V) by compound (I), can finish in a reactor, simplified operation, realize industrialization easily; Whole process does not need through column chromatography for separation, just can obtain high-quality two part of seeing through the purification process of routine, satisfies the suitability for industrialized production requirement.
Method of the present invention can be represented with following reaction formula:
R, R " are respectively C in the formula
1-C
8Alkyl or aryl.
1) in non-polar solvent, ferrocene under the catalyst (I) is 1 with acetylation reagent reaction, ferrocene (I) with the mol ratio of acetylation reagent: 1-5; Ferrocene (I) is 1 with the mol ratio of catalyzer: 1-3; Ferrocene (I) is 1 with the mol ratio of solvent: 5-15; Generated acetylferrocene (II) in 0-5 hour 0-100 ℃ of reaction; Reaction finishes, pours in the water, and the organic layer soda lye wash, the saturated common salt water washing, drying is directly used in the next step after concentrating;
Reaction formula is:
2) in solvent, acetylferrocene and reductive agent obtain compound ferrocene ethanol (III) in 25-100 ℃ of reaction 5-24 hour; The mol ratio of acetylferrocene and reductive agent is 1: 1-2, the mol ratio of acetylferrocene and solvent is 1: 5-10.
Reaction formula is:
3) ferrocene ethanol generates the acetoxyl group ethyl dicyclopentadienyl iron with alkaline matter catalysis and acetylizing agent in 20-100 ℃ of reaction esterification in 2-5 hour in solvent or when solvent-free; The mol ratio of solvent and compound ferrocene ethanol (III) is 5-10: 1, and the mol ratio of acetylizing agent and compound ferrocene ethanol (III) is 1-3: 1; The mol ratio of catalyzer and compound ferrocene ethanol (III) is 1-3: 1; Reaction is finished, and concentrating under reduced pressure reclaims solvent, and residue is treated down step usefulness.
Reaction formula is:
4) upwards go on foot and add organic solvent in the residue, dissolving is stirred, be cooled to 0-5 ℃, drop into dimethylamine agueous solution (30-50wt%), stirring at room reaction 2-5 hour, the mol ratio of solvent and compound acetyl oxygen ethyl dicyclopentadienyl iron is 5-10: 1, and the mol ratio of dimethylamine and compound acetyl oxygen ethyl dicyclopentadienyl iron is 1-5: 1; Reaction is finished, and concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron.
Reaction formula is:
5) with suitable solvent (as water or organic solvent) chiral acid is dissolved, add N, N dimethylamine base ethyl dicyclopentadienyl iron has been stirred to solid and has separated out, and with frozen water the fractionation system is cooled to 0-10 ℃, filters, and gets N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate.Wherein the mol ratio of solvent and chiral acid is 5-10: 1, and chiral acid and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-2: 1.
6) with N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate solvent recrystallization; Solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-5: 1;
7) product that step 6) is obtained is dissolved in the solvent, analyses with alkaline hydrolysis and obtains R-N, N dimethylamine base ethyl dicyclopentadienyl iron; Solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-5: 1; Alkali and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-1.5: 1;
Reaction formula is:
8) under nitrogen protection, down with R-N, N dimethylamine base ethyl dicyclopentadienyl iron is dissolved in the organic solvent ice-cooled, adds organolithium alkali, stirring reaction 2-5 hour, then reaction solution is cooled to-15--25C under, add dialkyl
1Phosphonium chloride finishes, and continues reaction after 2-5 hour, adds quencher in reaction system, and during stirring was fallen back, with extraction agent extraction three times, combining extraction liquid, drying concentrated, and residue gets the 1-S-dialkyl with solvent crystallization
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron; Wherein organolithium alkali and R-N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-2: 1; Dialkyl
1The mol ratio of phosphonium chloride and R-dimethylamino ethyl ferrocene is 1-3: 1, and solvent and R-N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-5: 1; Alkyl
1Be C
1-8Alkyl or aryl;
Reaction formula is:
Wherein R ' is C
1-8Alkyl or aryl.
9) with the 1-S-dialkyl
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron dissolves with Glacial acetic acid, adds dialkyl
2Phosphine, 20-100 ℃ of reaction 2-6 hour, reaction was finished, and concentrating under reduced pressure reclaims solvent, and residue gets the 1-S-dialkyl through Crystallization Separation
1Phosphino--2-R-dialkyl
2The phosphino-ferrocene; Dialkyl wherein
2Phosphine and 1-S-dialkyl
1Phosphine-2-R-N, the mol ratio of N dimethylamine base ferrocene is 1-2: 1; Glacial acetic acid and 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene and dialkyl
2The mol ratio of phosphine is 5-10: 1; Alkyl
2Be C
1-8Alkyl or aryl.
Reaction formula is:
Wherein R ', R " are respectively C
1-C
8Alkyl or aryl.
The used non-polar solvent of step 1) is sherwood oil, benzene, toluene, chloroform, methylene dichloride, ethylene dichloride or tetracol phenixin etc.;
The step 1) catalyst system therefor is the oxide compound of protonic acid, Lewis acid, alkali-metal oxide compound or alkaline-earth metal etc.;
The used acylating agent of step 1) is acetate, diacetyl oxide or Acetyl Chloride 98Min. etc.;
Step 2) solvent for use is that carbonatomss such as tetrahydrofuran (THF), ether, methyl alcohol, dehydrated alcohol, propyl alcohol are the Fatty Alcohol(C12-C14 and C12-C18) of 1-8;
Step 2) used reductive agent is borine, sodium borohydride, POTASSIUM BOROHYDRIDE, Lithium Aluminium Hydride or sodium Metal 99.5 etc. in;
The used catalyzer of step 3) is yellow soda ash, salt of wormwood, saleratus, sodium bicarbonate, volatile salt, diethylamine, triethylamine, pyridine, sodium alkoxide, potassium alcoholate, sodium hydride, potassium hydride KH or hydrolith etc.;
The used solvent of step 3) is water, methyl alcohol, ethanol, Virahol, sherwood oil, methylene dichloride, tetrahydrofuran (THF) or dioxane etc.;
The used acetylating agent of step 3) is glacial acetic acid, aceticanhydride or Acetyl Chloride 98Min. etc.;
The used solvent of step 4) is C
1-8Alcohol, as methyl alcohol, ethanol, propyl alcohol etc.
Step 2), the step 3) step 4) can finish in same reactor, can finish step by step.
The solvent that adopts in the step 5) is C
1-8Alcohol, acetone, water, tetrahydrofuran (THF), N, dinethylformamide or dioxane and they mixture between in twos.
The chiral acid resolving agent that adopts in the step 5) is D-tartrate, L-tartrate, D-camphorsulfonic acid, L-camphorsulfonic acid and the tartaric derivative of D-, L-, D-amygdalic acid or L-amygdalic acid.
Adopting recrystallization solvent in the step 6) is C
1-8Alcohol, acetone, water, tetrahydrofuran (THF), N, dinethylformamide or dioxane and they mixture between in twos.
Adopting solvent in the step 7) is C
1-8Alcohol, acetone, water, tetrahydrofuran (THF), N, dinethylformamide or dioxane and they mixture between in twos.
To analyse the alkali of employing be salt of wormwood, yellow soda ash, saleratus, sodium bicarbonate, volatile salt, diethylamine, triethylamine, sodium alkoxide, potassium alcoholate, sodium hydride, potassium hydride KH or hydrolith to alkali in the step 7).
The solvent that is adopted in the step 8) is sherwood oil, ether, tetrahydrofuran (THF) or methyl tertiary butyl ether etc.
The organolithium alkali that is adopted in the step 8) is strong organic basess such as lithium alkylide, amido lithium or phenyl lithium.
The dialkyl that is adopted in the step 8)
1Phosphonium chloride is a diphenyl phosphine chloride etc.;
Compound in the step 8) (VI) is 1 with the mol ratio of solvent: 1-5; Compound (VI) is 1 with the mol ratio of lithium alkali: 1-2; Compound (VI) and dialkyl group
1The phosphonium chloride mol ratio is 1: 1-3;
Temperature of reaction in the step 8) is-15 ℃-25 ℃; Reaction times is 2-5 hour.
The dialkyl that is adopted in the step 9)
2Phosphine is two (3, the 5-3,5-dimethylphenyl) phosphine, dicyclohexylphosphontetrafluoroborate, di-t-butyl phosphine or diphenylphosphine etc.
Adopting method of the present invention system is raw material from the ferrocene of cheapness, need not column chromatography, and by effective simple and easy method of the synthetic biphosphine ligand of simple organic reaction, this method productive rate height, cost are low, have industrial utility value.
Embodiment
In order to understand the present invention better, further illustrate content of the present invention below in conjunction with embodiment, but content of the present invention not only is confined to the following examples.
Embodiment 1:
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
Add 18.6g ferrocene (I), 14g aluminum chloride, 60ml sherwood oil in the there-necked flask that is connected to mechanical stirring, backflow, dropping funnel of 250ml, beginning slowly drips the 11ml Acetyl Chloride 98Min., drips off in about 30 minutes.50 ℃ down reaction after 4 hours reaction solution is poured in the water, divide and get organic layer, water layer extracts with organic solvent dichloromethane, merges organic layer, drying, concentrate the pure acetylferrocene (II) of about 21g, yield 92%.Fusing point 83-85 ℃.
1H?NMR(CDCl
3)：δ4.77(s，2H)，4.50(s，2H)，4.21(s，4H)，2.40(s，3H)；
13C?NMR(CDCl)：δ201.9，79.0，72.2，69.7，69.4，27.2。
Two) preparation of ferrocene ethanol (III)
In 250ml single port bottle, add 22.8g acetylferrocene (II), 38ml methyl alcohol, 5.4g POTASSIUM BOROHYDRIDE.60 ℃ down reaction in reactor, add the 9ml Glacial acetic acid after 4 hours, add the extraction of ethyl acetate and water, the organic layer drying concentrates and reclaims solvent, must the pure ferrocene ethanol (III) of about 21g, yield 91%.Fusing point 74-75 ℃.
1H?NMR(CDCl
3)：δ4.48(s，1H)，4.26(s，9H)，1.77(s，1H)，1.43(d，J＝4.5Hz，3H)；
13C?NMR(CDCl
3)：δ94.6，68.2，67.9，67.8，66.1，66.0，65.4，23.8。
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
In 250ml single port bottle, add 20g ferrocenyl ethanol (III) and 13ml aceticanhydride, the 16ml pyridine, the 55ml methylene dichloride, reaction system is after reacting 5 hours under 30 ℃, reaction system extracts with ethyl acetate and water, the organic layer drying is after concentrating under reduced pressure reclaims solvent, the acetyl oxygen ethyl dicyclopentadienyl iron (IV) that the about 22.7g of residue is pure, yield 96%.Fusing point 64-66 ℃.
1H?NMR(CDCl
3)：δ1.45(d，3H，J＝6.5Hz)，1.85(d，3H，J＝4.5Hz)，4.12-4.33(m，9H)，4.56(dq，1H，J＝4.5/6.5Hz)；
13C?NMR(CDCl
3)：δ23.7，65.5，66.0，66.1，67.8(d)，67.9，68.2，94.7。
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
The acetyl oxygen ethyl dicyclopentadienyl iron (IV) that in 250ml single port bottle, adds 27.2g, the 34ml dissolve with methanol stirs, be cooled to 0-5 ℃, drop into the dimethylamine agueous solution of 18ml 50wt%, stirring at room reaction 4 hours, reaction is finished, concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V), collect the about 18g of 110 ℃/10mmHg cut, yield 70%.
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In 250ml single port bottle, add 51.4 gram N, N dimethylamine base ethyl dicyclopentadienyl iron (V), 30.0 gram D-(+)-tartrate and 100 milliliters of ethanol, stirring and refluxing dissolving.After having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, and gets solid 30 grams.
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron (V) chirality hydrochlorate
To go up the step solid and drop in 250 milliliters of single port flasks, and reflux with 100 ml methanol and dissolve, and after having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, dry solid 27 grams that get.
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
To go up step gained solid and dissolve with 100 ml waters, the adding massfraction is 40% sodium hydroxide solution, and pH is transferred to 8-9, has oily matter to generate, and adds ethyl acetate extraction, merges organic layer, concentrates the recovery solvent, and the residue underpressure distillation gets 15 grams.[α]
D 25=+14.1
0(c=1.6, ethanol).
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Eight) 1-S-diphenylphosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Add 3.6 gram R-N in reaction flask, 15 milliliters of N dimethylamine base ethyl dicyclopentadienyl iron (V) and anhydrous diethyl ethers under nitrogen protection, add the butyllithium of 12.4 milliliters (1.4M).Reaction is 2 hours under the room temperature, adds 10 milliliters of diethyl ether solutions of the diphenyl phosphine chloride of 6.2 grams then, and back flow reaction is 4 hours then, be cooled to 0-5 ℃, add 20 milliliters of saturated sodium bicarbonate solutions, static layering, water layer extracts with benzene, merges organic layer, uses anhydrous sodium sulfate drying, concentrate, add 10 milliliters of acetone in the residue, have solid to separate out, filter, dry that product 2.7 restrains, yield is 44%.Fusing point 141-143 ℃, [α]
D 25=-360.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3)：δ1.19(d，3H，J＝3Hz)，1.77(s，6H)，3.9(s，5H)，3.56-4.39(m，4H)，6.88-7.71(cm，10H)。
Nine) preparation of 1-S-diphenylphosphine-2-R-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII)
With 2g1-S-diphenylphosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI) adds 2.2g two (3 with the dissolving of 1ml Glacial acetic acid, the 5-3,5-dimethylphenyl) phosphine, after 5 hours, concentrating under reduced pressure reclaims solvent 60 ℃ of reactions, and residue adds 10 milliliters of acetone stirrings and separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII), filter, the dry 2.6g that gets, yield is 90%, fusing point is 183-187 ℃, [α]
D 25=-338.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3，500MHz)：δ1.46(m，3H)，2.19(s，6H)，2.27(s，6H)，3.72(m，1H)，3.84(s，5H)，4.03(m，2H)，4.24(m，1H)，6.77(m，1H)，6.85-7.00(m，5H)，7.10-7.20(m，5H)，7.35-7.45(m，3H)，7.60-7.70ppm(m，2H)。
31P?NMR(CDCl
3)：δ-25.2(d，J＝19Hz)，6.5ppm(d，J＝19Hz)。
Embodiment 2
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
In the there-necked flask that is connected to mechanical stirring, backflow, dropping funnel of 250ml, add 18.6g ferrocene (I), 12g aluminum oxide, 60ml methylene dichloride, drip the 21ml Acetyl Chloride 98Min. in 30 minutes.60 ℃ down reaction after 5 hours reaction solution is poured in the 100ml water, divide and get organic layer, water layer extracts with organic solvent dichloromethane, merges organic layer, drying, concentrate the pure acetylferrocene (II) of about 21.9g, yield 96%.Fusing point 83-85 ℃.
1H?NMR(CDCl
3)：δ4.77(s，2H)，4.50(s，2H)，4.21(s，4H)，2.40(s，3H)；
13C?NMR(CDCl)：δ201.9，79.0，72.2，69.7，69.4，27.2。
Two) preparation of ferrocene ethanol (III)
In 250ml single port bottle, add 21.9g acetylferrocene (II), 38ml methyl alcohol, 2.3g sodium, 60 ℃ are reacted after 4 hours down, in reactor, add the 6ml Glacial acetic acid, add the extraction of ethyl acetate and water, the organic layer drying concentrates and reclaims solvent, must the pure ferrocene ethanol (III) of about 20g, yield 90%.Fusing point 74-75 ℃.
1H?NMR(CDCl
3)：δ4.48(s，1H)，4.26(s，9H)，1.77(s，1H)，1.43(d，J＝4.5Hz，3H)；
13C?NMR(CDCl
3)：δ94.6，68.2，67.9，67.8，66.1，66.0，65.4，23.8。
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
In 250ml single port bottle, add 20g ferrocenyl ethanol (III) and 9ml Acetyl Chloride 98Min., the 18ml triethylamine, the 40ml dehydrated alcohol, reaction system is after reacting 5 hours under 30 ℃, reaction system extracts with ethyl acetate and water, the organic layer drying is after concentrating under reduced pressure reclaims solvent, the acetyl oxygen ethyl dicyclopentadienyl iron (IV) that the about 22g of residue is pure, yield 93%.Fusing point 64-66 ℃.
1H?NMR(CDCl
3)：δ1.45(d，3H，J＝6.5Hz)，1.85(d，3H，J＝4.5Hz)，4.12-4.33(m，9H)，4.56(dq，1H，J＝4.5/6.5Hz)；
13C?NMR(CDCl
3)：δ23.7，65.5，66.0，66.1，67.8(d)，67.9，68.2，94.7。
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
The acetyl oxygen ethyl dicyclopentadienyl iron (IV) that in 250ml single port bottle, adds 22.6g, the 34ml dissolve with ethanol stirs, be cooled to 0-5C, drop into the dimethylamine agueous solution of 15ml 50wt%, stirring at room reaction 4 hours, reaction is finished, concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V), collect the about 14.9g of 110 ℃/10mmHg cut, yield 70%.
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In 250ml single port bottle, add 51.4 gram N, N dimethylamine base ethyl dicyclopentadienyl iron (V), 69.6 gram D-(+)-camphorsulfonic acid and 100 ml waters, stirring and refluxing dissolving.After having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, and gets solid 30 grams
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron (V) chirality hydrochlorate
To go up the step solid and drop in 250 milliliters of single port flasks, and with 100 milliliters of alcohol reflux dissolvings, after having dissolved, stop to heat, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, and is dry that solid 27 restrains.
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
To go up step gained solid and dissolve with 100 milliliters of dioxane, the adding massfraction is 40% sodium carbonate solution, and pH is transferred to 8-9, has oily matter to generate, and adds ethyl acetate extraction, merges organic layer, concentrates the recovery solvent, and the residue underpressure distillation gets 15 grams.[α]
D 25=+14.1
0(c=1.6, ethanol).
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl?
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Eight) 1-S-diphenylphosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Add 3.6 gram R-N in reaction flask, 15 milliliters of N dimethylamine base ethyl dicyclopentadienyl iron (V) and anhydrous tetrahydro furans under nitrogen protection, add 3 gram lithium diisopropyl amidos.Reaction is 2 hours under the room temperature, adds 10 milliliters of diethyl ether solutions of the diphenyl phosphine chloride of 6.2 grams then, and back flow reaction is 4 hours then, be cooled to 0-5 ℃, add 20 milliliters of saturated sodium bicarbonate solutions, static layering, water layer extracts with benzene, merges organic layer, uses anhydrous sodium sulfate drying, concentrate, add 10 milliliters of acetone in the residue, have solid to separate out, filter, dry that product 2.8 restrains, yield is 45%.Fusing point 141-143 ℃, [α]
D 25=-360.5
0(c=0.6, CHCl
3).
1HNMR(CDCl
3)：δ1.19(d，3H，J＝3Hz)，1.77(s，6H)，3.9(s，5H)，3.56-4.39(m，4H)，6.88-7.71(cm，10H)。
Nine) preparation of 1-S-diphenylphosphine-2-R-dicyclohexylphosphontetrafluoroborate ferrocene (VII)
With 2g 1-S-diphenylphosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI) dissolves with the 1ml Glacial acetic acid, add the 2.7g dicyclohexylphosphontetrafluoroborate, after 5 hours, concentrating under reduced pressure reclaims solvent 60 ℃ of reactions, residue adds 10 milliliters of acetone stirrings and separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII) filters, the dry 2.4g that gets, yield is 88%, [α]
D 25=-368.6
0(c=0.6, CHCl
3)
1H?NMR(CDCl
3)：δ0.92-1.22(br?m，11Cy?H)，1.34-1.72(br?m，11Cy?H)，1.54(dd，J＝7，3，3H)，3.13(qd，J＝2，2，lH)，3.77(s，5Cp?H)，3.93-3.97(m，1Cp?H)，4.20-4.25(m，1Cp?H)，4.28-4.33(m，1Cp?H)，7.07-7.18(m，5Ph?H)，7.26-7.34(m，3Ph?H)，7.54-7.62(m，2Ph，H)；
31P?NMR(CDCl
3)δ+15.7(d，Jpp＝30，PCy
2)，-25.8(d，PPh
2)。
Embodiment 3:
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
In the there-necked flask that is connected to mechanical stirring, backflow, dropping funnel of 250ml, add 18.6g ferrocene (I), 13.6g zinc chloride, 60ml toluene, slowly drip the 21ml Acetyl Chloride 98Min. in 30 minutes.60 ℃ down reaction after 5 hours reaction solution is poured in the 100ml water, divide and get organic layer, water layer extracts with organic solvent dichloromethane, merges organic layer, drying, concentrate the pure acetylferrocene (II) of about 22g, yield 96.5%.Fusing point 83-85 ℃.
1H?NMR(CDCl
3)：δ4.77(s，2H)，4.50(s，2H)，4.21(s，4H)，2.40(s，3H)；
13C?NMR(CDCl)：δ201.9，79.0，72.2，69.7，69.4，27.2。
Two) preparation of ferrocene ethanol (III)
In 25ml single port bottle, add 2.28g acetylferrocene (II), 4ml tetrahydrofuran (THF), the tetrahydrofuran solution of the borine of 10ml 1mol/L.25 ℃ down reaction in reactor, add the 0.6ml Glacial acetic acid after 8 hours, add the extraction of ethyl acetate and water, the organic layer drying, concentrate reclaim solvent must the pure ferrocene ethanol (III) of about 2g, yield 90%.Fusing point 74-75 ℃.
1H?NMR(CDCl
3)：δ4.48(s，1H)，4.26(s，9H)，1.77(s，1H)，1.43(d，J＝4.5Hz，3H)；
13C?NMR(CDCl
3)：δ94.6，68.2，67.9，67.8，66.1，66.0，65.4，23.8。
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
In 250ml single port bottle, add 23g ferrocenyl ethanol (III) and 9ml acetic acid, 7.2g sodium hydride, the 50ml methylene dichloride, reaction system is after reacting 5 hours under 30 ℃, reaction system extracts with ethyl acetate and water, the organic layer drying is after concentrating under reduced pressure reclaims solvent, the acetyl oxygen ethyl dicyclopentadienyl iron (IV) that the about 24.5g of residue is pure, yield 90%.Fusing point 64-66 ℃.
1H?NMR(CDCl
3)：δ1.45(d，3H，J＝6.5Hz)，1.85(d，3H，J＝4.5Hz)，4.12-4.33(m，9H)，4.56(dq，1H，J＝4.5/6.5Hz)；
13C?NMR(CDCl
3)：δ23.7，65.5，66.0，66.1，67.8(d)，67.9，68.2，94.7。
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
The acetyl oxygen ethyl dicyclopentadienyl iron (IV) that in 250ml single port bottle, adds 27.2g, the 40ml anhydrous alcohol solution stirs, be cooled to 0-5 ℃, drop into the dimethylamine agueous solution of 18ml 50wt%, stirring at room reaction 4 hours, reaction is finished, concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V), collect the about 17.5g of 110 ℃/10mmHg cut, yield 68%.
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In 250ml single port bottle, add 51.4 gram N, N dimethylamine base ethyl dicyclopentadienyl iron (V), 30.0D-(+)-tartrate and 100 ml methanol, stirring and refluxing dissolving.After having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters to such an extent that solid 30 restrains
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron (V) chirality hydrochlorate
To go up the step solid and drop in 250 milliliters of single port flasks, and reflux with 100 milliliters of tetrahydrofuran (THF)s and dissolve, and after having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, dry solid 27 grams that get.
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
To go up step gained solid and dissolve with 100 ml waters, the adding massfraction is 40% sodium hydrogen carbonate solution, and pH is transferred to 8-9, has oily matter to generate, and adds ethyl acetate extraction, merges organic layer, concentrates the recovery solvent, and the residue underpressure distillation gets 15 grams.[α]
D 25=+14.1
0(c=1.6, ethanol).
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Eight) 1-S-diphenylphosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Add 3.6 gram R-N in reaction flask, 15 milliliters of N dimethylamine base ethyl dicyclopentadienyl iron (V) and anhydrous methyl tertiary butyl ethers under nitrogen protection, add the butyllithium of 12.4 milliliters (1.4M).Reaction is 2 hours under the room temperature, adds 10 milliliters of diethyl ether solutions of the diphenyl phosphine chloride of 6.2 grams then, and back flow reaction is 4 hours then, be cooled to 0-5 ℃, add 20 milliliters of saturated sodium bicarbonate solutions, static layering, water layer extracts with benzene, merges organic layer, uses anhydrous sodium sulfate drying, concentrate, add 10 milliliters of acetone in the residue, have solid to separate out, filter, dry that product 2.8 restrains, yield is 45%.Fusing point 141-143 ℃, [α]
D 25=-360.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3)：δ1.19(d，3H，J＝3Hz)，1.77(s，6H)，3.9(s，5H)，3.56-4.39(m，4H)，6.88-7.71(cm，10H)。
Nine) preparation of 1-S-diphenylphosphine-2-R-di-t-butyl phosphine ferrocene (VII)
With 2g1-S-diphenylphosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI) dissolves with the 1ml Glacial acetic acid, add 2.0g di-t-butyl phosphine, after 5 hours, concentrating under reduced pressure reclaims solvent 60 ℃ of reactions, and residue adds 10 milliliters of acetone stirrings and separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII), filter, the dry 2.1g that gets, yield is 83%.[α]
D 25＝-417.1
0(c＝0.6，CHCl
3)。
1H?NMR(CDCl
3)：δ0.92(d，J＝7，9H)，1.12(d，J＝7，9H)，1.78(dd，J＝7，3，3H)，3.37(qd，J＝7，2，1H)，3.77(s，5Cp?H)，3.90-3.95(m，1Cp?H)，4.14-4.18(m，1Cp?H)，4.29-4.33(m，1Cp?H)，7.06-7.21(m，5Ph?H)，7.25-7.33(m，3Ph?H)，7.52-7.62(m，2Ph?H)；
31P?NMR(CDCl
3)δ+49.9(d，Jpp＝50，P(t-Bu)
2)，-26.1(d，PPh
2)。
Embodiment 4:
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
In the there-necked flask that is connected to mechanical stirring, backflow, dropping funnel of 250ml, add 18.6g ferrocene (I), 28ml aceticanhydride, 20ml chloroform, slowly drip 30ml 85wt% phosphoric acid in 30 minutes.40 ℃ down reaction after 5 hours reaction solution is poured in the l00ml water, add dichloromethane extraction, organic layer anhydrous magnesium sulfate drying, concentrated the pure acetylferrocene (II) of about 19.4g, yield 85%.Fusing point 83-85 ℃.
1H?NMR(CDCl
3)：δ4.77(s，2H)，4.50(s，2H)，4.21(s，4H)，2.40(s，3H)；
13C?NMR(CDCl)：δ201.9，79.0，72.2，69.7，69.4，27.2。
Two) preparation of ferrocene ethanol (III)
In 250ml single port bottle, add 22.8g acetylferrocene (II), 50ml propyl alcohol, 5.2g POTASSIUM BOROHYDRIDE.70 ℃ down reaction in reactor, add the 9ml Glacial acetic acid after 3 hours, add the extraction of ethyl acetate and water, the organic layer drying, concentrate reclaim solvent must the pure ferrocene ethanol (III) of about 20g, yield 87%.Fusing point 74-75 ℃.
1H?NMR(CDCl
3)：δ4.48(s，1H)，4.26(s，9H)，1.77(s，1H)，1.43(d，J＝4.5Hz，3H)；
13C?NMR(CDCl
3)：δ94.6，68.2，67.9，67.8，66.1，66.0，65.4，23.8。
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
In 250ml single port bottle, add 23g ferrocenyl ethanol (III) and 15ml aceticanhydride, 11.2g potassium tert.-butoxide, the 30ml methylene dichloride, reaction system is after reacting 5 hours under 30 ℃, reaction system extracts with ethyl acetate and water, the organic layer drying is after concentrating under reduced pressure reclaims solvent, the acetyl oxygen ethyl dicyclopentadienyl iron (IV) that the about 22.6g of residue is pure, yield 82%.Fusing point 64-66 ℃.
1H?NMR(CDCl
3)：δ1.45(d，3H，J＝6.5Hz)，1.85(d，3H，J＝4.5Hz)，4.12-4.33(m，9H)，4.56(dq，1H，J＝4.5/6.5Hz)；
13C?NMR(CDCl
3)：δ23.7，65.5，66.0，66.1，67.8(d)，67.9，68.2，94.7。
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
The acetyl oxygen ethyl dicyclopentadienyl iron (IV) that in 250ml single port bottle, adds 22.6g, the 30ml dissolve with methanol stirs, be cooled to 0-5 ℃, drop into the dimethylamine agueous solution of 23ml 33wt%, stirring at room reaction 5 hours, reaction is finished, concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V), collect the about 14.9g of 110 ℃/10mmHg cut, yield 70%.
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In 250ml single port bottle, add 51.4 gram N, N dimethylamine base ethyl dicyclopentadienyl iron (V), 45.6 gram D-(+)-amygdalic acid and 100 milliliters of acetone, stirring and refluxing dissolving.After having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters to such an extent that solid 30 restrains
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron (V) chirality hydrochlorate
To go up the step solid and drop in 250 milliliters of single port flasks, with 100 milliliters of N, dinethylformamide refluxes and dissolves, and after having dissolved, stops heating, and slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, dry solid 27 grams that get.
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
To go up step gained solid with 100 milliliters of dissolve with ethanol, and add massfraction and be 20% alcohol sodium solution, pH is transferred to 8-9, and have oily matter to generate, and add ethyl acetate extraction, and merge organic layer, and concentrate and reclaim solvent, the residue underpressure distillation gets 15 and restrains.[α]
D 25=+14.1
0(c=1.6, ethanol).
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Eight) 1-S-diphenylphosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Add 3.6 gram R-N in reaction flask, 15 milliliters of N dimethylamine base ethyl dicyclopentadienyl iron (V) and anhydrous diethyl ethers under nitrogen protection, add the phenyl lithium of 2.3 grams.Reaction is 2 hours under the room temperature, adds 10 milliliters of diethyl ether solutions of the diphenyl phosphine chloride of 6.2 grams then, and back flow reaction is 4 hours then, be cooled to 0-5 ℃, add 20 milliliters of saturated sodium bicarbonate solutions, static layering, water layer extracts with benzene, merges organic layer, uses anhydrous sodium sulfate drying, concentrate, add 10 milliliters of acetone in the residue, have solid to separate out, filter, dry that product 2.7 restrains, yield is 44%.Fusing point 141-143 ℃, [α]
D 25=-360.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3)：δ1.19(d，3H，J＝3Hz)，1.77(s，6H)，3.9(s，5H)，3.56-4.39(m，4H)，6.88-7.71(cm，10H)。
Nine) preparation of 1-S-diphenylphosphine-2-R-diphenylphosphine ferrocene (VII)
With 2g1-S-diphenylphosphine-2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI) dissolves with the 1ml Glacial acetic acid, add the 2.5g diphenylphosphine, after 5 hours, concentrating under reduced pressure reclaims solvent 60 ℃ of reactions, residue adds 10 milliliters of acetone stirrings and separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII) filters, the dry 2.2g that gets, yield is 82%, [α]
D 25=-355.5
0(c=1.0, CHCl
3).
1H?NMR(CDCl
3)：δ1.58(dd，J＝7，7，3H)，3.95(qd，J＝2，2，1H)，3.96(s，qd，5Cp?H)，4.12(m，1Cp?H)，4.18(m，1Cp?H)，4.34(t，J＝2.5，1Cp?H)，7.20-7.53(m，16Ph?H)，7.74-7.85(m，4Ph?H)；
31P?NMR(CDCl
3)δ+5.9(d，Jpp＝20.6，CHPPh
2)，-25.8(d，CpPPh
2)。
Embodiment five:
The synthetic method of biphosphine ligand, realize by following step:
One) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In the there-necked flask that is connected to mechanical stirring, backflow, dropping funnel of 250ml, add 18.6g ferrocene (I), 10g zinc oxide, 60ml methylene dichloride, slowly drip the 21ml Acetyl Chloride 98Min. in 30 minutes.Reaction was poured reaction solution in the water into after 5 hours under 60 ℃, divided and got organic layer, and water layer extracts with organic solvent dichloromethane, merged organic layer, and drying concentrates, adding 40ml methyl alcohol in residue, 5.4gKBH
460 ℃ are reacted after 4 hours down, in reactor, add the 9ml Glacial acetic acid, add the extraction of ethyl acetate and water, the organic layer drying, concentrate and reclaim solvent, 14ml aceticanhydride in residue, 16ml Anhydrous potassium carbonate, the 60ml sherwood oil, reaction is after 5 hours down in 30 ℃ for reaction system, and reaction system extracts with ethyl acetate and water, and the organic layer drying is after concentrating under reduced pressure reclaims solvent, adding the 40ml dissolve with methanol in residue stirs, be cooled to 0-5 ℃, slowly drop into the dimethylamine agueous solution of 33ml 33%, stirring at room reaction 4 hours, reaction is finished, concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V), collect the about 20.5g of 110 ℃/10mmHg cut, yield 80%.
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Two) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
In 250ml single port bottle, add 51.4 gram N, N dimethylamine base ethyl dicyclopentadienyl iron (V), 30.0 gram D-(+)-tartrate and 100 ml methanol, stirring and refluxing dissolving.After having dissolved, stop heating, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, filters, and gets solid 30 grams.With 100 ml methanol backflow dissolving, after having dissolved, stop to heat, slowly cooling per hour reduces by 2 ℃, has solid to separate out after 24 hours, and filtration is dry that solid 27 restrains.With 100 milliliters of acetone solutions, add the potassium tert.-butoxide solid, pH is transferred to 8-9, there is oily matter to generate, add ethyl acetate extraction, merge organic layer, concentrate and reclaim solvent, the residue underpressure distillation gets 23 grams, and yield is 45%.[α]
D 25=+14.1
0(c=1.6, ethanol).
1H?NMR(CDCl
3)：δ4.08-4.03(m，9H)，3.54(q，J＝6.9Hz，1H)，2.02(s，6H)，1.38(d，J＝7.2Hz，3H)；
13C?NMR(CDCl
3)：δ87.5，69.8，69.0，67.8，67.6，67.3，59.1，41.0，16.5。
Three) preparation of 1-S-diphenylphosphine-2-R-dimethylamino ethyl ferrocene (VI)
Add 3.6 gram R-N in reaction flask, 15 milliliters of N dimethylamine base ethyl dicyclopentadienyl iron (V) and anhydrous diethyl ethers under nitrogen protection, add the butyllithium of 12.4 milliliters (1.4M).Reaction is 2 hours under the room temperature, adds 10 milliliters of diethyl ether solutions of the diphenyl phosphine chloride of 6.2 grams then, back flow reaction is 4 hours then, is cooled to 0-5 ℃, adds 20 milliliters of saturated sodium bicarbonate solutions, static layering, water layer extracts with benzene, merges organic layer, use anhydrous sodium sulfate drying, concentrate, add 10 milliliters of acetone in the residue, there is solid to separate out, filter, dry that product 2.8 restrains, yield is 45%.Fusing point 141-143 ℃, [α]
D 25=-360.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3)：δ1.19(d，3H，J＝3Hz)，1.77(s，6H)，3.9(s，5H)，3.56-4.39(m，4H)，6.88-7.71(cm，10H)。
Four) preparation of 1-S-diphenylphosphine-2-R-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII)
With 2g S-1-diphenylphosphino-R-2-N, N dimethylamine base ferrocene (VI) adds 2.2g two (3 with the dissolving of 1ml Glacial acetic acid, the 5-3,5-dimethylphenyl) phosphine, after 5 hours, concentrating under reduced pressure reclaims solvent 60 ℃ of reactions, and residue adds 10 milliliters of acetone stirrings and separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII), filter, the dry 2.6g that gets, yield is 90%, fusing point is 183-187 ℃, [α]
D 25=-338.5
0(c=0.6, CHCl
3).
1H?NMR(CDCl
3)：δ1.46(m，3H)，2.19(s，6H)，2.27(s，6H)，3.72(m，1H)，3.84(s，5H)，4.03(m，2H)，4.24(m，1H)，6.77(m，1H)，6.85-7.00(m，5H)，7.10-7.20(m，5H)，7.35-7.45(m，3H)，7.60-7.70ppm(m，2H)。
31P?NMR(CDCl
3)：δ-25.2(d，J＝19Hz)，6.5ppm(d，J＝19Hz)。
Embodiment six:
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
In non-polar solvent, the following and acetylizing agent reaction of catalyst, the mol ratio of non-polar solvent and ferrocene (I) is 5: 1, the mol ratio of catalyzer and ferrocene (I) is 3: 1; Generated acetylferrocene (II) in 5 hours 0 ℃ of reaction; Reaction finishes, and reaction solution is poured in the water, divides and gets organic layer, and the water layer organic solvent extraction merges organic layer, and drying is directly used in the next step after concentrating.
Used non-polar solvent is a tetracol phenixin; Used catalyzer is alkaline earth metal oxide (as a magnesium oxide); Used acetylizing agent is an acetic acid.
Two) preparation of ferrocene ethanol (III)
With a certain amount of acetylferrocene dissolution with solvents, add reductive agent in 25 ℃ of reactions 24 hours, obtain ferrocene ethanol (III); The mol ratio of reductive agent and acetylferrocene (II) is 1: 1, and the mol ratio of solvent and acetylferrocene (II) is 5: 1, and reaction is finished, and concentrates and reclaims solvent, and residue is directly used in the next step.
Used solvent is a sherwood oil; Reductive agent is a Lithium Aluminium Hydride.
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
Upwards go on foot and add solvent, catalyzer and acetylation reagent in the residue, generate the acetoxyl group ethyl dicyclopentadienyl iron in 5 hours acidylates of 20 ℃ of reactions; The mol ratio of solvent and compound ferrocene ethanol (III) is 5: 1; The mol ratio of acetylation reagent and compound ferrocene ethanol (III) is 3: 1; The mol ratio of catalyzer and ferrocene ethanol (III) is 3: 1; Reaction is finished, and concentrating under reduced pressure reclaims solvent, and residue is treated down step usefulness.
Used solvent is a Virahol; Used catalyzer is the Carbon Dioxide ammonium; Used acetylation reagent is an aceticanhydride.
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
Upwards go on foot and add suitable solvent in the residue, dissolving is stirred, be cooled to 0 ℃, drop into the 50wt% dimethylamine agueous solution, stirring at room reaction 5 hours, the mol ratio of solvent and compound acetyl oxygen ethyl dicyclopentadienyl iron (IV) is 5: 1, and compound acetyl oxygen ethyl dicyclopentadienyl iron (IV) is 1: 1 with the mol ratio of dimethylamine; Reaction is finished, and concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V).
Used solvent is C
1-8Alcohol (as n-propyl alcohol).
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
With suitable solvent chiral acid is dissolved, add N, N dimethylamine base ethyl dicyclopentadienyl iron (V), stir half an hour, have solid to separate out, the fractionation system is cooled to about 10 ℃ with cold water, filter, solid with a small amount of solvent wash the N of chiral acid, N dimethylamine base ethyl dicyclopentadienyl iron salt (V).Wherein solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron (V) is 5: 1; Chiral acid and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron (V) is 1: 1.
Used solvent is C
1-8Alcohol (as ethanol); Used chiral acid resolving agent is the D-camphorsulfonic acid.
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron (V) chirality hydrochlorate
N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V) heat up and to be dissolved in the suitable solvent, cool to suitable temp and get optically pure N, and N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V), this salt are treated down the step parsing.Solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V) is 1: 1.
Used solvent is an acetone.
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
With N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V) is dissolved in the suitable solvent, the aqueous solution that adds alkali stirs and treats that solid dissolves fully, and dissolving is finished, reaction solution is poured in the water, extract combining extraction liquid, concentrating under reduced pressure with reaction solvent, residue is chirality R-N, N dimethylamine base ethyl dicyclopentadienyl iron (V).Wherein solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V) is 5: 1; Alkali and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate (V) is 1: 1, the mol ratio of extraction agent and salt is 5: 1.
Solvent for use is C
1-8Alcohol (as methyl alcohol); Used alkali is triethylamine; The solvent of extraction is a sherwood oil.
Eight) 1-S-alkyl
1Phosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Under nitrogen protection, to R-N, add organolithium alkali in the solution of N dimethylamine base ethyl dicyclopentadienyl iron (V) down ice-cooled, stirring reaction 2 hours is cooled to reaction solution under-25 ℃ then, adds dialkyl
1Phosphonium chloride finishes, and continues reaction after 2 hours, adds quencher in reaction system, stirs half an hour, pours in the water, and with extraction agent extraction three times, combining extraction liquid, drying concentrates, and residue gets the 1-S-dialkyl with solvent crystallization
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI).R-N wherein, N dimethylamine base ethyl dicyclopentadienyl iron (V) is 1: 1 with the mol ratio of organolithium alkali; R-N, N dimethylamine base ethyl dicyclopentadienyl iron (V) and dialkyl
1The mol ratio of phosphonium chloride is 1: 1, R-N, and N dimethylamine base ethyl dicyclopentadienyl iron (V) is 1: 1 with the mol ratio of solvent.
Used dialkyl
1Phosphonium chloride is a diphenyl phosphine chloride; Used solvent is a sherwood oil; The organolithium alkali that is adopted is phenyl lithium; The solvent of extraction is an ethyl acetate.
Nine) 1-S-dialkyl
1Phosphine-2-R-dialkyl
2The preparation of phosphine ferrocene (VII)
With the 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) adds dialkyl with the Glacial acetic acid dissolving
2Phosphine, 20 ℃ of reactions 6 hours, reaction was complete, and concentrating under reduced pressure reclaims solvent, and residue adding acetone stirs separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII), filters the dry S-1-dialkyl that gets
1Phosphino--R-2-dialkyl
2Phosphino-ferrocene (VII).1-S-dialkyl wherein
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) and dialkyl
2The mol ratio of phosphine is 1: 1; The 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) is 1: 5 with the mol ratio of acetic acid.
Used dialkyl
2Phosphine is two (3, the 5-3,5-dimethylphenyl) phosphine.
Embodiment seven:
The synthetic method of biphosphine ligand, realize by following step:
One) acetylferrocene (II) is synthetic
In non-polar solvent, the following and acetylizing agent reaction of catalyst, the mol ratio of non-polar solvent and ferrocene (I) is 15: 1, the mol ratio of catalyzer and ferrocene (I) is 3: 1; Generated acetylferrocene (II) in 1 hour 100 ℃ of reactions; Reaction finishes, and reaction solution is poured in the water, divides and gets organic layer, and the water layer organic solvent extraction merges organic layer, and drying is used for the next step after concentrating.
Used non-polar solvent is an ethylene dichloride; Catalyst system therefor acid is inorganic acid (as sulfuric acid); Used acetylizing agent is an aceticanhydride.
Two) preparation of ferrocene ethanol (III)
(II) uses dissolution with solvents with a certain amount of acetylferrocene, adds reductive agent in 100 ℃ of reactions 5 hours, obtains ferrocene ethanol (III); The mol ratio of reductive agent and acetylferrocene (II) is 2: 1, and the mol ratio of solvent and acetylferrocene (II) is 10: 1, and reaction is finished, and concentrates and reclaims solvent, and residue is directly used in the next step.
Used solvent is an ether; Reductive agent is a sodium Metal 99.5.
Three) preparation of acetyl oxygen ethyl dicyclopentadienyl iron (IV)
Upwards go on foot and add solvent, catalyzer and acetylation reagent in the residue, generate acetoxyl group ethyl dicyclopentadienyl iron (IV) in 2 hours acidylates of 100 ℃ of reactions; The mol ratio of solvent and compound ferrocene ethanol (III) is 10: 1; The mol ratio of acetylation reagent and compound ferrocene ethanol (III) is 3: 1; The mol ratio of catalyzer and ferrocene ethanol (III) is 3: 1; Reaction is finished, and concentrating under reduced pressure reclaims solvent, and residue is treated down step usefulness.
Used solvent is a tetrahydrofuran (THF); Used catalyzer is sodium alkoxide (as a sodium ethylate); Used acetylation reagent is an Acetyl Chloride 98Min..
Four) N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
Upwards go on foot and add suitable solvent in the residue, dissolving is stirred, be cooled to 5 ℃, drop into the 33wt% dimethylamine agueous solution, stirring at room reaction 2 hours, the mol ratio of solvent and compound acetyl oxygen ethyl dicyclopentadienyl iron (IV) is 10: 1, and compound acetyl oxygen ethyl dicyclopentadienyl iron (IV) is 1: 5 with the mol ratio of dimethylamine; Reaction is finished, and concentrating under reduced pressure reclaims solvent, the residue underpressure distillation collect N, N dimethylamine base ethyl dicyclopentadienyl iron (V).
Used solvent is C
1-8Alcohol (as the trimethyl carbinol).
Five) N, the fractionation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
With suitable solvent chiral acid is dissolved, add N, N dimethylamine base ethyl dicyclopentadienyl iron (V), stir half an hour, have solid to separate out, the fractionation system is cooled to about 10 ℃ with cold water, filter, solid with a small amount of solvent wash N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate.Wherein solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron (V) is 10: 1; Chiral acid and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron (V) is 2: 1.
Used solvent is a tetrahydrofuran (THF); Used chiral acid resolving agent is the D-amygdalic acid.
Six) N, the recrystallization of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate
N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate heat up and to be dissolved in the suitable solvent, cool to suitable temp and get optically pure N, and N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate, this salt are treated down the step parsing.The mol ratio of solvent and salt is 5: 1.
Used solvent is a tetrahydrofuran (THF).
Seven) R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (V)
With N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is dissolved in the suitable solvent, the aqueous solution that adds alkali stirs and treats that solid dissolves fully, and dissolving is finished, reaction solution is poured in the water, extract combining extraction liquid, concentrating under reduced pressure with reaction solvent, residue is R-N, N dimethylamine base ethyl dicyclopentadienyl iron (V).Wherein solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 10: 1; The mol ratio of alkali and salt is 1.5: 1, and the mol ratio of extraction agent and salt is 10: 1.
Solvent for use is N, dinethylformamide; Used alkali is potassium hydride KH; The solvent of extraction is a toluene.
Eight) 1-S-dialkyl
1Phosphine-2-R-N, the preparation of N dimethylamine base ethyl dicyclopentadienyl iron (VI)
Under nitrogen protection, to R-N, add organolithium alkali in the solution of N dimethylamine base ethyl dicyclopentadienyl iron (V) down ice-cooled, stirring reaction 5 hours is cooled to reaction solution under-15 ℃ then, adds dialkyl
1Phosphonium chloride finishes, and continues reaction after 5 hours, adds quencher in reaction system, stirs half an hour, pours in the water, and with extraction agent extraction three times, combining extraction liquid, drying concentrates, and residue gets the 1-S-dialkyl with solvent crystallization
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron (VI).R-N wherein, N dimethylamine base ethyl dicyclopentadienyl iron (V) is 1: 2 with the mol ratio of organolithium alkali; R-N, N dimethylamine base ethyl dicyclopentadienyl iron (V) and dialkyl
1The mol ratio of phosphonium chloride is 1: 3, R-N, and N dimethylamine base ethyl dicyclopentadienyl iron (V) is 1: 5 with the mol ratio of solvent.
Used dialkyl
1Phosphonium chloride is a diphenyl phosphine chloride; Used solvent is a tetrahydrofuran (THF); The organolithium alkali that is adopted is amido lithium (as lithium diisopropyl amido); The solvent of extraction is a benzene.
Nine) 1-S-dialkyl
1Phosphine-2-R-dialkyl
2The preparation of phosphine ferrocene (VII)
With the 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) adds dialkyl with the Glacial acetic acid dissolving
2Phosphine, 100 ℃ of reactions 2 hours, reaction was complete, and concentrating under reduced pressure reclaims solvent, and residue adding acetone stirs separates out S-1-diphenylphosphino-R-2-two (3, the 5-3,5-dimethylphenyl) phosphine ferrocene (VII), filters the dry 1-S-dialkyl that gets
1Phosphine-2-R-dialkyl
2Phosphine ferrocene (VII).1-S-dialkyl wherein
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) and dialkyl
2The mol ratio of phosphine is 1: 2; The 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene (VI) is 1: 10 with the mol ratio of acetic acid.
Used dialkyl
2Phosphine is the di-t-butyl phosphine.
The bound value and the interval value of each raw material of the present invention can both be realized the present invention, and each cited raw material can both realize the present invention, just do not enumerate embodiment one by one at this.
Claims (13)
1. the synthetic method of chiral ferrocene diphosphine ligand is characterized in that, is realized by following step:
1) in non-polar solvent, ferrocene and acetylizing agent generated acetylferrocene in 0-5 hour 0-100 ℃ of reaction under the catalyst; The mol ratio of catalyzer and ferrocene is 1-3: 1; The mol ratio of non-polar solvent and ferrocene is 5-15: 1; The mol ratio of acetylation reagent and ferrocene is 1-5: 1;
2) with the acetylferrocene dissolution with solvents, add reductive agent in 25-100 ℃ of reaction 5-24 hour, obtain ferrocene ethanol; Wherein the mol ratio of reductive agent and acetylferrocene is 1-2: 1, and the mol ratio of solvent and acetylferrocene is 5-10: 1;
3) in ferrocene ethanol, add solvent, catalyzer and acetylation reagent, generate the acetoxyl group ethyl dicyclopentadienyl iron in 2-5 hour acidylate of 20-100 ℃ of reaction; Solvent and compound ferrocene alcoholic acid mol ratio are 5-10: 1; Acetylation reagent and compound ferrocene alcoholic acid mol ratio are 1-3: 1; Catalyzer and ferrocene alcoholic acid mol ratio are 1-3: 1;
4) add organic solvent in the acetoxyl group ethyl dicyclopentadienyl iron, stirring and dissolving is cooled to 0-5 ℃, and adding massfraction is the dimethylamine agueous solution of 30%-50%, and stirring at room reaction 2-5 hour obtains N, N dimethylamine base ethyl dicyclopentadienyl iron; The mol ratio of solvent and acetyl oxygen ethyl dicyclopentadienyl iron is 5-10: 1, and the mol ratio of dimethylamine and acetyl oxygen ethyl dicyclopentadienyl iron is 1-5: 1;
5) chiral acid is dissolved in water or the organic solvent, stirs adding N down, N dimethylamine base ethyl dicyclopentadienyl iron finishes, and continues to be stirred to solid to separate out, and is cooled to 0-10 ℃ then, filters, and obtains N, the chirality hydrochlorate of N dimethylamine base ethyl dicyclopentadienyl iron; Wherein solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 5-10: 1; Chiral acid and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-2: 1;
6) with N, N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate solvent recrystallization; Solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-5: 1;
7) product that step 6) is obtained is dissolved in the solvent, analyses with alkaline hydrolysis and obtains R-N, N dimethylamine base ethyl dicyclopentadienyl iron; Solvent and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-5: 1; Alkali and N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron chirality hydrochlorate is 1-1.5: 1;
8) under nitrogen protection, down with R-N, N dimethylamine base ethyl dicyclopentadienyl iron is dissolved in the organic solvent ice-cooled, adds organolithium alkali, stirring reaction 2-5 hour, then reaction solution is cooled to-15--25 ℃ under, add dialkyl
1Phosphonium chloride finishes, and continues reaction after 2-5 hour, adds quencher in reaction system, and during stirring was fallen back, with extraction agent extraction three times, combining extraction liquid, drying concentrated, and residue gets the 1-S-dialkyl with solvent crystallization
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron; Wherein organolithium alkali and R-N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-2: 1; Dialkyl
1The mol ratio of phosphonium chloride and R-dimethylamino ethyl ferrocene is 1-3: 1, and solvent and R-N, the mol ratio of N dimethylamine base ethyl dicyclopentadienyl iron is 1-5: 1; Alkyl
1Be C
1-8Alkyl or aryl;
9) with the 1-S-dialkyl
1Phosphino--2-R-N, N dimethylamine base ethyl dicyclopentadienyl iron dissolves with Glacial acetic acid, adds dialkyl
2Phosphine, 20-100 ℃ of reaction 2-6 hour, reaction was finished, and concentrating under reduced pressure reclaims solvent, and residue gets the 1-S-dialkyl through Crystallization Separation
1Phosphino--2-R-dialkyl
2The phosphino-ferrocene; Dialkyl wherein
2Phosphine and 1-S-dialkyl
1Phosphine-2-R-N, the mol ratio of N dimethylamine base ferrocene is 1-2: 1; Glacial acetic acid and 1-S-dialkyl
1Phosphine-2-R-N, N dimethylamine base ferrocene and dialkyl
2The mol ratio of phosphine is 5-10: 1; Alkyl
2Be C
1-8Alkyl or aryl.
2. synthetic method according to claim 1 is characterized in that: the used non-polar solvent of step 1) is sherwood oil, benzene, toluene, chloroform, methylene dichloride, ethylene dichloride or tetracol phenixin.
3. synthetic method according to claim 1 and 2 is characterized in that: the step 1) catalyst system therefor is the oxide compound of protonic acid, Lewis acid, basic metal or alkaline-earth metal; The used acylating agent of step 1) is acetate, diacetyl oxide or Acetyl Chloride 98Min..
4. synthetic method according to claim 1 and 2 is characterized in that: step 2) solvent for use is that tetrahydrofuran (THF), ether or carbonatoms are the Fatty Alcohol(C12-C14 and C12-C18) of 1-8.
5. synthetic method according to claim 1 and 2 is characterized in that: step 2) in used reductive agent be borine, sodium borohydride, POTASSIUM BOROHYDRIDE, Lithium Aluminium Hydride or sodium Metal 99.5.
6. synthetic method according to claim 1 and 2 is characterized in that: the used catalyzer of step 3) is yellow soda ash, salt of wormwood, saleratus, sodium bicarbonate, volatile salt, diethylamine, triethylamine, pyridine, sodium alkoxide, potassium alcoholate, sodium hydride, potassium hydride KH or hydrolith; The used solvent of step 3) is water, methyl alcohol, ethanol, Virahol, sherwood oil, methylene dichloride, tetrahydrofuran (THF) or dioxane; The used acetylation reagent of step 3) is glacial acetic acid, aceticanhydride or Acetyl Chloride 98Min..
7. synthetic method according to claim 1 and 2 is characterized in that: the used organic solvent of step 4) is C
1-8Alkyl alcohol.
8. synthetic method according to claim 1 and 2 is characterized in that: the organic solvent that adopts in the step 5) is C
1-8Alkyl alcohol, acetone, tetrahydrofuran (THF), N, dinethylformamide or dioxane, or the mixture of wherein appointing both.
9. synthetic method according to claim 1 and 2 is characterized in that: the chiral acid that adopts in the step 5) is D-tartrate, L-tartrate, D-camphorsulfonic acid, L-camphorsulfonic acid and the tartaric derivative of D-, the tartaric derivative of L-, D-amygdalic acid or L-amygdalic acid.
10. synthetic method according to claim 1 and 2 is characterized in that: the recrystallization solvent for use is C in the step 6)
1-8Alkyl alcohol, acetone, water, tetrahydrofuran (THF), N, dinethylformamide or dioxane, or the mixture of wherein appointing both.
11. synthetic method according to claim 1 and 2 is characterized in that: to analyse the alkali of employing be salt of wormwood, yellow soda ash, saleratus, sodium bicarbonate, volatile salt, diethylamine, triethylamine, sodium alkoxide, potassium alcoholate, sodium hydride, potassium hydride KH or hydrolith to alkali in the step 7); Used solvent is C in the step 7)
1-8Alkyl alcohol, acetone, water, tetrahydrofuran (THF), N, dinethylformamide or dioxane, or the mixture of wherein appointing both.
12. synthetic method according to claim 1 and 2 is characterized in that: the organic solvent that is adopted in the step 8) is sherwood oil, ether, tetrahydrofuran (THF) or methyl tertiary butyl ether; The organolithium alkali that is adopted in the step 8) is lithium alkylide, amido lithium or phenyl lithium; The dialkyl that is adopted in the step 8)
1Phosphonium chloride is a diphenyl phosphine chloride.
13. synthetic method according to claim 1 and 2 is characterized in that: the dialkyl that is adopted in the step 9)
2Phosphine is two (3, the 5-3,5-dimethylphenyl) phosphine, dicyclohexylphosphontetrafluoroborate, di-t-butyl phosphine or diphenylphosphine.
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